This invention relates to pre-filled drug delivery devices, and in particular to devices for attachment to the skin of a subject having a needle for penetration of the skin of the subject.
WO 97/21457, which is incorporated herein by reference, discloses a liquid drug delivery device having a base member defining a skin-contacting surface for application to the skin of a subject. A columnar cartridge serving as a reservoir for the drug is connected to the base member such that in use the longitudinal axis of the cartridge is disposed substantially parallel to the skin-contacting surface. A delivery needle communicates in use with the interior of the cartridge and is adapted to penetrate the skin of the subject, and there is provided means for expelling a drug out of the interior of the cartridge and through the skin of the subject via the delivery needle.
It has been found that adapting conventional cartridges (such as cartridges for pen-type insulin injectors, or other drug cartridges well known in the art) so as to enable an expelling means to expel the drug therefrom, and so as to enable communication with a delivery needle forming part of such a device, increases the costs of the cartridge considerably, and this in turn adds to the cost of the overall device and hence its attractiveness to consumers. The main reason for this is that conventional drug cartridges are relatively inexpensive, but redesigning such a component and changing the manufacturing process, or individually modifying such components drives costs up considerably.
Nevertheless, in technical terms, the devices of WO 97/21457 have undoubted advantages over the prior art due to the fact that the disposition of the cartridge parallel to the skin enables the device to be applied to the skin and worn unobtrusively during drug delivery. Both application of the device and delivery of the drug can be accomplished in a single step requiring little or no manual dexterity.
A further problem associated with the devices of WO 97/21457 is in relation to the delivery needle which effectively extends at right angles to the axis of the cartridge. This may be accomplished by using a conduit arrangement leading from the cartridge to a conventional needle, or by means of a right-angled needle which extends from an end of the cartridge co-axially with the axis of the cartridge and then bends through a right angle to penetrate the skin. The latter arrangement is preferred since it reduces the number of parts and the complexity of the device. However, it may prove difficult to bend a needle while maintaining sterility (which is of course essential), since the sterility of the needle is assured by a protective sheath which extends the entire length of the needle and which may be damaged in the bending process.
For devices which employ a needle to penetrate the skin there is a danger that after use the device may accidentally infect the patient or others if not properly disposed of Our WO 95/13838 discloses an intradermal device of this type having a displaceable cover which is moved between a first position in which the needle is retracted before use and a second position in which the needle is exposed during use. Removal of the device from the skin causes the cover to return to the first position in which the needle is again retracted before disposal.
The present invention aims to decrease the possibilities that the needle could become exposed by accident before or after use for example by a child playing with the device if not properly disposed of. Clearly given the risks associated with infectious diseases, particularly those carried by blood, any possibility of accidental infection must be minimised to the utmost and preferably eliminated entirely. Some of the features of devices according to the invention which address these problems are set out below, and further advantages will become apparent from the following description.
In devices of the present invention, a conventional syringe barrel is mounted relative to a base member defining a skin-contacting surface, with the longitudinal axis of the needle substantially parallel to the skin-contacting surface in use.
The invention provides a base member defining a skin-contacting surface for application to the skin of a subject;
a syringe serving as a reservoir for the drug and which is connected to the base member such that in use the longitudinal axis of the syringe is disposed substantially parallel to the skin-contacting surface;
a delivery needle in communication with the syringe, the needle having an angled bend which directs the tip of the needle substantially perpendicular to the skin-contacting surface such that in use the tip of the needle is adapted to penetrate the skin of the subject; and
means for expelling a drug out of the interior of the syringe.
Preferably, the syringe is a pre-filled syringe.
By employing a conventional syringe, preferably a pre-filled syringe, the devices of the present invention avoid the need for custom-designed components for which it may be difficult to obtain regulatory approval and manufacturing validation from bodies such as the U.S. Food and Drug Administration (F.D.A.) and similar other national bodies.
It has been found that while conventional drug-containing components such as cartridges and pre-filled syringes are relatively inexpensive, redesigning such components and changing the manufacturing process, or individually modifying such components drives costs up considerably for the device as a whole, which decreases the attractiveness of such devices to customers. Thus, devices of the present invention which employ widely available syringe bodies will be advantageous over corresponding devices which include a non-standard drug chamber.
Preferably, a mounting member is mounted along the length of the exterior of the needle at the angled portion. Such a mounting member serves two purposes: firstly it acts as a mounting point for a seal or sheath to ensure sterility of the portion of the needle which will contact or penetrate the skin, and secondly it may assist in the correct bending of the needle during the manufacturing process.
Preferably, the mounting member is permanently affixed to the needle.
Further, preferably, a sealing sheath is mounted on the mounting member.
The sheath is preferably removably mounted on the mounting member.
Preferably, means are provided for driving a piston along the interior of the syringe barrel, and these means are also mounted relative to the skin-contacting surface. Preferably, both the syringe barrel and the driving means are mounted within a housing.
In preferred embodiments, the driving means is disposed alongside the syringe barrel rather than at the end thereof, as this arrangement may lead to a more ergonomic design, as well as to advantages in the manner in which the driving means may be actuated as will be explained below in greater detail.
Preferably, the driving means is a gas generator.
Suitably, a tube provides communication between the gas generator and a piston in the syringe.
In one embodiment, the needle extends from the neck of the syringe barrel parallel to the longitudinal axis of the syringe and then bends to a substantially right angle, such that the tip of the needle points perpendicularly to the longitudinal axis of the syringe.
Preferably, the sealing sheath is provided with a flexible pull tab which extends through a release liner.
Further, preferably, when the pull tab is pulled away from the base member, the release liner is pulled away from a lower surface of the base member and the sealing sheath is detached from the mounting member to reveal the needle tip.
In one embodiment, the base member is pivotally mounted to a housing of the device.
Preferably, the device is provided with a removable locking member such as a semi-rigid safety tab which prevents relative movement of the base member towards the housing following removal of the sealing sheath and the release liner, thereby retaining the needle within the housing until skin penetration is required.
Further, preferably, relative motion of the housing towards the base member causes activation of the gas generator while optionally simultaneously causing the needle tip to penetrate the skin.
Preferably, the base member is displaceable relative to the housing between a first position in which the needle is concealed from the exterior of the device and a second position in which the delivery needle protrudes from the device for penetration of the skin, the device further comprising means for locking the device in the first position after a single reciprocation of the device from the first position to the second position and back to the first position.
In this embodiment preferably the locking means comprises a mechanical latch which is brought into operation by said reciprocation.
In an especially preferred embodiment said latch comprises a pair of elements mounted on the base member and the housing respectively, said elements being shaped such that they can have two relative configurations when the base member is in said first position relative to the housing, namely a movable configuration in which the elements are mutually movable, and a locked configuration in which the elements are prevented from mutual movement, and wherein reciprocation of the base member and the housing causes the elements to pass from the first movable configuration, through an intermediate configuration when the base member is in said second position relative to the housing, and then to said locked configuration, thereby preventing any further movement of the base member relative to the housing.
Also preferably one of said elements is provided with a recess which is adapted to receive a projection on the other of said elements, the recess and the projection being spaced apart from one another in the movable configuration, and being in engagement with one another in the locked configuration.
Further, preferably, movement of the base member relative to the housing is initially prevented by said removable locking member.
Still further, preferably, the presence of said removable locking member also prevents the means for providing a gas from being actuated.
The removable locking member preferably comprises a laminar member inserted between said base member and said housing.
In a preferred embodiment following delivery of drug through the needle, any residual gas is vented through a release valve.
In one embodiment means are provided for enabling a user to determine that delivery of drug has been completed.
In a further embodiment, the syringe barrel is provided with an end piston in addition to an internal piston so as to allow for mixing of a drug in a lyophilised form with a diluent, said internal piston initially dividing the interior of the syringe barrel into a diluent compartment and a drug compartment.
Preferably, the pressure resulting from the gas generator is transmitted through the diluent compartment so as to push the internal piston into the drug compartment allowing for ingress of diluent into said drug compartment.
In a further preferred embodiment a travel limiting mechanism is provided to limit the maximum amount of travel of the internal piston along the length of the syringe barrel so that the dose of drug can be adjusted to suit individual user needs.
It will be appreciated that the locking means described herein is capable of having a broad application in drug delivery devices having a drug delivery needle.
Thus in a further embodiment the invention provides a drug delivery device comprising:
a housing having an internal drug reservoir;
a drug delivery needle extending from the housing for penetration of the skin of a subject, the needle having an outlet for drug delivery;
a base member defining a skin-contacting surface for application to the skin of a subject, said base member being displaceable relative to the housing between a first position in which the needle is concealed from the exterior of the device and a second position in which the delivery needle protrudes from the device for penetration of the skin, the device further comprising means for locking the device in the first position after a single reciprocation of the device from the first position to the second position and back to the first position.
Preferably, the base member is pivotally mounted to the housing.
Preferably, the locking means comprises a mechanical latch which is brought into operation by said reciprocation.
Also preferably, said latch comprises a pair of elements mounted on the base member and the housing respectively, said elements being shaped such that they can have two relative configurations when the base member is in said first position relative to the housing, namely a movable configuration in which the elements are mutually movable, and a locked configuration in which the elements are prevented from mutual movement, and wherein reciprocation of the base member and the housing causes the elements to pass from the first movable configuration, through an intermediate configuration when the base member is in said second position relative to the housing, and then to said locked configuration, thereby preventing any further movement of the base member relative to the housing.
Further, preferably, one of said elements is provided with a recess which is adapted to receive a projection on the other of said elements, the recess and the projection being spaced apart from one another in the movable configuration, and being in engagement with one another in the locked configuration.
Still further, preferably, movement of the base member relative to the housing is initially prevented by said removable locking member.
The invention also includes a method of manufacturing and filling drug delivery devices in which a syringe barrel is filled with a drug under sterile conditions, with the fluid path and the skin-contacting andxe2x80x94penetrating portion of the needle also sealed or sheathed under sterile conditions. After this is completed, the remainder of the manufacturing and assembly steps can be carried out in a clean area (as opposed to a sterile area) since the sealed pre-filled syringe barrel remains sterile.
Thus, the invention provides a method for manufacturing and filling a drug delivery device comprising:
providing a base member having a skin-contacting surface; a syringe having drug therein and which is connected to the base member such that in use the longitudinal axis of the syringe is disposed substantially parallel to the skin-contacting surface; a delivery needle in communication with the syringe, the needle having an angled bend which directs the tip of the needle substantially perpendicular to the skin-contacting surface such that in use the tip of the needle is adapted to penetrate the skin of the subject; and means for expelling a drug out of the interior of the syringe, filling the syringe barrel with the drug under sterile conditions with the drug delivery path and the skin-contacting and skin-penetrating portions of the needle under sterile conditions and carrying out the remainder of the manufacturing and assembly steps in a clean area.
The term xe2x80x9cclean areaxe2x80x9d denotes an area of high cleanliness as would be expected for manufacturing medical devices. The term xe2x80x9csterile areaxe2x80x9d denotes a higher standard of cleanliness (i.e. sterility) such as is required for areas in which syringes are pre-filled. While medical devices must be assembled in clean areas according to well defined standards, the level of cleanliness is not as stringent as for a filling suite in which parenteral drug containers are filled. By pre-filling and sealing all parts of the fluid path, one obtains a component which can be assembled with other components under normal clean area conditions.
Preferably, the sterility of the drug delivery path and the skin-contacting and skin-penetrating portions of the needle is achieved by securely affixing a mounting member along the exterior length of the needle under sterile conditions.
Further, preferably, the drug delivery path and the skin-contacting and skin-penetrating portions of the needle are sealed by means of a sheath mounted on the mounting member.
Preferably, the external mounting member is used as a bending point when a right-angled needle is required.
The sterility of portion of the needle adjacent the needle tip may be assured by securely affixing a mounting member along the exterior length of the needle and ensuring that the mounting member and needle are sterile, following which a sheath or seal is mounted on the mounting member. Subsequent steps of manufacture can then be carried out on the needle without compromising sterility. For example, the external mounting member can be used as a bending point if a right-angled needle is required.
Because of the difficulties in manipulating axially unsymmetric components on a mass-production line, particularly where an unsymmetric part of the component protrudes sideways from an otherwise regular device (e.g. a syringe barrel with a bent needle extending perpendicularly for skin penetration) it is desirable to bend the needle as late as possible in the assembly process.
Conversely, because the sheath guarantees sterility, it is desirable to sheath the needle as early as possible in the manufacturing process (since remaining steps can be carried out in the less expensive clean area).
However, when a seal or sheath is mounted on the neck of the barrel to cover the needle, it is difficult to bend the needle without damaging the sheath and compromising sterility. Equally, it is difficult to mount a sheath on a bent needle since the manipulation may be difficult and the tip of the needle is likely to damage the sheath. Thus, the use of a sterile sheath and the requirement of a bent needle give rise to a conflict as to the most desirable method of manufacture.
The use of a mounting member solves this problem in two respects. Firstly, it enables the sheath to be applied at an early stage (during the filling of the syringe barrel, for example). The sterile barrel can then be removed from the sterile area for further manufacturing/assembly steps. Secondly, the needle can be bent with the sheath intact without having to contact the sheath and risk damage. The needle can be held by the mounting point and bent, and this step can be carried out in a clean environment without any risk to the sterility of the fluid path or the portion of the needle which penetrates or contacts the skin.
In a further aspect the invention provides a method of delivering drug to a subject comprising the steps of:
providing a drug delivery device having a skin-contacting surface, a syringe having drug therein, and which is connected to the base member such that in use the longitudinal axis of the syringe is disposed substantially parallel to the skin contacting surface, a delivery needle in communication with the syringe, the needle having an angled bend, and means for expelling a drug out of the interior of the syringe;
applying the device to the skin of the subject; and
activating the device.
Preferably, the tip of the delivery needle is substantially perpendicular to the skin contacting surface such that in use the tip of the needle is adapted to penetrate the skin of the subject.
Also preferably, the the means for expelling the drug comprises a gas generator.
Further, preferably, the syringe is prefilled.
Also preferably the device is activated by moving the housing towards the base member.
Preferably, the movement of the housing simultaneously causes the needle to penetrate the skin.
Further, preferably, the method comprises the step of causing the device to lock into position after use whereby the needle tip is recessed within the housing.
Other objects, features and advantages of the present invention will become apparent upon reading the following detailed description of the embodiments of the invention, when taken in conjunction with the drawings and appended claims.